The goal of the project is to increase knowledge of the chemical structures of glycoprotein hormones and to relate the information gained to an understanding of their function in the body. The primary interest of the laboratory concerns two hormones, luteinizing hormone (LH) and thyroid-stimulating hormone (TSH) as well as related glycoproteins from both primate and non-primate mammalian species. Chemical investigations of the related glycoproteins will be carried out with particular emphasis placed on bovine FSH. Specific aims include determination of the disulfide bonding in the subunits of these molecules and investigation of the three dimensional structure both by chemical modification and by a search for crystalline derivatives suitable for X-ray diffraction studies. After knowledge of chemical structure is complete, major objectives become investigation of the contributions of various portions of the molecule (including the carbohydrate) to the hormonal activity of TSH and to make chemical modifications which will aid in an understanding of thyroid physiology and treatment of disorders of the thyroid gland. Interactions of these derivatives with receptor preparations will also be studied. Another objective is to prepare glycoprotein hormones (including human) of better antigenic purity than present available in order to improve immunological studies on the relationships between these hormones. BIBLIOGRAPHIC REFERENCES: "Structure and Structure-Function Relationships in Glycoprotein Hormones". J. G. Pierce, M.R. Faith, L.C. Giudice and J.R. Reeve, Ciba Foundation Symposium 41 (new series), Elsevier/Excerpta Medica/North-Holland, pp 225-250 (1976). "Amino Acid Sequences of Proteins--Hormones of the Anterior Pituitary and Placenta" John G. Pierce, CRC Handbook of Biochemistry and Molecular Biology (G.D. Fasman, ed.), 3rd Edition, Proteins Vol. III, pp 385-398 (1976).